Development of thresholds and a visualization tool for use of a blood test in routine clinical dementia practice.
Level 3 - non-randomized controlled study
Multi-cohort observational diagnostic accuracy and biomarker tool derivation-validation study.
PubMed 39096164 · doi:10.1002/alz.14088
What was done
Plasma biomarkers (phosphorylated tau181 [P-tau181], amyloid-beta [Abeta] 42/40 ratio, glial fibrillary acidic protein [GFAP], and neurofilament light [NfL]) were measured using Simoa assays across 1,199 participants. Investigators used LASSO regression to select optimal biomarkers and receiver operating characteristic (ROC) curves to evaluate diagnostic performance. The selected panel and cutoffs were validated in two independent cohorts, and a clinical visualization tool based on UpSet and density plots was developed.
What was found
LASSO selected P-tau181, GFAP, and NfL. The combined panel achieved an area under the ROC curve (AUC) of 83% for identifying amyloid positivity in pre-dementia stages, an AUC of 87% to 89% for distinguishing Alzheimer's disease or controls from frontotemporal dementia, and an AUC of 74% to 76% for distinguishing Alzheimer's disease or controls from dementia with Lewy bodies. These diagnostic AUCs demonstrated reproducibility across the two independent validation cohorts.
Why it matters
This study provides a practical, multi-marker plasma interpretation framework with graphical diagnostic tools to support differential diagnosis of neurodegenerative dementias in routine clinical practice.
Limits
The abstract does not specify the exact sample sizes of the two independent validation cohorts, nor does it detail participant demographic composition or reference standard adjudication methods. Diagnostic performance was lower for dementia with Lewy bodies (AUC 74%-76%), and the tool has not yet been evaluated prospectively for clinical utility or real-world decision-making.
Cited by
- supports A biomarker profile of normal p-tau, normal GFAP, and elevated neurofilament light (NfL) in blood is commonly associated with frontotemporal dementia.